Technology update

Jun 6, 2012

Nanopores detect nucleosome substructures

Researchers at the Delft University of Technology in the Netherlands have succeeded in detecting nucleosome substructures using nanopores. The measurements are made in liquid and require no labelling, which means that the technique might be used to rapidly identify a variety of disease markers, such as those for cancer and lupus, in biological cells.

The human body contains a staggering 100 trillion cells. If all the strands of DNA contained within these cells were placed end to end, they would stretch 600 times the distance between the Sun and the Earth. Nucleosomes play a crucial role in “condensing” this entire DNA so that it fits inside our bodies. For example, in a single cell, about 2 m of DNA is packaged around spools of nucleosomes to fit into a cell nucleus that is just 10 µm in size.

Nucleosomes can break down into protein substructures, which, depending on the circumstances, are “signatures” of healthy cell function or early markers for a variety of diseases. Cees Dekker and Gautam Soni have now shown that they can use nanopore technology to detect various nucleosome substructures that could thus prove useful for studying disease progression in human cells.

As their name suggests, nanopores are nanometre-sized holes in thin solid-state membranes. Ions flow through the pores if a voltage is applied across these membranes when they are immersed in an ionic solution. This ion flow constitutes an electric current.

If nucleosomes are present in the ionic fluid, they travel through the pores producing tiny fluctuations in the pore current that can be picked up by a very sensitive electronic set-up. The size of these fluctuations and how long they last can be used to glean information about the structural state of the nucleosome and whether it is complete or fragmented into various substructures.

Probing disease markers

“Our technique could be employed to detect nucleosome states involved in a variety of diseases,” Soni told nanotechweb.org, “and we are currently working on modifying the nanopore experiments to more directly probe specific disease markers in patient samples.”

The work also provides a possible route to study nucleosome positions along specific regions of human chromosomes that could help us detect a range of genetic diseases, he adds.

The researchers say that they would now like to use the nanopore technique to detect more sophisticated processes, like functional changes in cells caused by alterations to nucleosome structure by chromatin remodelling enzymes, for example.